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Immunomodulation by virulence proteins of the parapoxvirus orf virus
Abstract:
Three orf virus putative virulence proteins are described that exhibit immunomodulatory functions. The OVIFNR gene at the left terminus of the viral genome encodes an interferon resistance protein with homology to the E3L gene of vaccinia virus. OVIFNR functions by preventing a dsRNA-dependent kinase from inhibiting virus and cell protein synthesis as part of the interferon-induced anti-viral state within infected cells. The orf virus orthologue of the ovine interleukin-10 (vIL-10) gene is located at the right terminus of the viral genome. Both vIL-10 and host (ovine) IL-10 function in vitro as inhibitors of pro-inflammatory cytokine production by keratinocytes and macrophages, and both inhibit IFN-gamma production from activated peripheral blood lymphocytes. Both the orf virus vIL-10 and ovine IL-10 stimulate mast cell and thymocyte proliferation. In this respect the orf virus IL-10 differs from Epstein Barr virus IL-10 which does not exhibit cell proliferative activity. Finally, the orf virus GM-CSF inhibitory factor gene (GIF) at the right terminus of the viral genome encodes an inhibitor of GM-CSF that also binds IL-2. Together, these viral proteins are capable of inhibiting key components of the ovine anti-virus immune and inflammatory response.
Insights
Orf virus virulence proteins OVIFNR, vIL-10, and GIF suppress the ovine immune response. These proteins inhibit interferon, reduce pro-inflammatory cytokines, and block granulocyte-macrophage colony-stimulating factor, aiding viral evasion.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Orf virus (ORFV) is a significant pathogen in livestock.
- Understanding ORFV virulence mechanisms is crucial for developing control strategies.
- Viral proteins often modulate host immune responses to facilitate infection.
Purpose of the Study:
- To identify and characterize orf virus proteins involved in immune modulation.
- To elucidate the functional mechanisms of these viral proteins in the context of the host immune response.
Main Methods:
- Gene identification and characterization of ORFV virulence genes.
- In vitro assays to assess protein functions, including inhibition of cytokine production and cell proliferation.
- Homology analysis with known viral immune evasion proteins.
Main Results:
- The OVIFNR gene encodes an interferon resistance protein that prevents dsRNA-dependent kinase inhibition.
- Orf virus vIL-10 inhibits pro-inflammatory cytokine production and IFN-gamma, while stimulating mast cell and thymocyte proliferation.
- The GIF gene product inhibits GM-CSF and binds IL-2, further suppressing immune responses.
Conclusions:
- Orf virus utilizes multiple proteins (OVIFNR, vIL-10, GIF) to counteract key ovine antiviral and inflammatory responses.
- These viral proteins collectively inhibit crucial components of the host innate and adaptive immunity.
- The identified virulence factors provide targets for future antiviral interventions against orf virus.